Project Summary Our overarching goal is to arrest the HIV epidemic and its negative impact on young people in sub Saharan African (SSA) through improving the uptake, retention and adherence of multi-level combination HIV prevention by AGYW and male partners. South Africa has an estimated 6.3 million people living with HIV ? the highest in the world. Despite having the largest HIV treatment program in the world, HIV incidence in Adolescent Girls and Young Women (AGYW aged 15-24) remains extremely high. Whilst there have been significant innovations in combination HIV prevention, e.g. universal test and treat (UTT) and Pre-exposure prophylaxis (PrEP), this has far outpaced the ability to deliver them. To control the HIV epidemic here is an urgent to significantly improve uptake and retention of HIV prevention by AGYW and male partners, alongside UTT of those testing positive. In this project we have a unique opportunity to leverage a key time-sensitive events in a poor and rural hyperendemic area of KwaZulu-Natal: The roll out of eight new youth-focused multi- level HIV prevention interventions for AGYW and their male partners by PEPFAR?s Determined, Resilient, Empowered, AIDS free, Mentored, and Safe (DREAMS) program in the context of a state of the art demographic and health surveillance, where data on individual HIV biomarkers, sexual behaviors, HIV prevention and ART exposure are linked to public-sector clinical records for HIV and other care. We will achieve this through three interlinked aims: Specific aim 1: Quantify how multiple levels of social dynamics interact to predict uptake of DREAMS components. Approach: We will use hierarchical analysis of population surveillance data to evaluate how community, household and interpersonal-level exposures predict uptake of each intervention, and two composite outcome measures: 1) Exposure to community-level DREAMS interventions, 2) uptake of the individual-level HIV care and prevention. Specific aim 2: Elucidate how individuals? life-course transitions and exposure to DREAMS affect retention and adherence to HIV care and prevention. Approach: We will use both survival analysis of the population surveillance data and in-depth qualitative interviews to evaluate how specific life-course events affect HIV prevention and care cascade trajectories and how community-level DREAMS exposures moderate the impact of life-course transitions on adherence and retention. Specific aim 3: Ascertain whether family- and peer-network strategies improve uptake and adherence to combination prevention interventions by young people. Approach: we will work with youth to adapt existing models of community and peer-support to develop an intervention informed by aims 1 and 2. We will pilot the acceptability and feasibility of this approach on improving AGYW and male peers uptake and retention of HIV care and prevention. Our multidisciplinary team includes HIV epidemiologists, a biostatistician, social scientists, psychologist and intervention development expertise from the Africa Health Research Institute, University College London, Southampton and the London School of Hygiene and Tropical Medicine. Moving forward, this will provide answers to an NIH priority area: Can using peer, family and community-level networks harness the full mortality and HIV incidence reducing potential of multi-level HIV prevention for adolescents and young people in rural SSA?